The University of Pittsburgh Medical Center's Sexually Transmitted Infections (STI) Collaborative Research Center will conduct research with a primary focus on prevention of female reproductive tract damage due to sexually transmitted microbial agents. This program brings together a multidisciplinary group of researchers, with both clinical and basic research expertise in the field of STIs. The UPMC STI CRC will conduct research to determine methods of prevention of female reproductive tract damage due to STIs. It will do so through a set of four interrelated and thematically linked research projects, each reflecting the particular research strengths of the Project Leaders/Principal Investigators (PI). Project 1 (Wiesenfeld, PI) will determine the importance of anti-anaerobic therapy in the treatment of women with acute PID. Project 2 (Hillier, PI) will determine the role of novel organisms in acute endometritis. Project 3 (Darville, PI) will determine the role of Toll-like receptor 2 signaling in innate and adaptive responses to Chlamydiae. Project 4 (Cherpes, PI) will determine protective T cell responses to Chlamydia trachomatis infection. Several specific areas of interest called for in the STI CRC funding opportunity announcement will be addressed by work outlined in this U19 proposal including: (1) development of treatment strategies for STIs, (2) research that provides a better understanding of vaginal ecology, including interactions between vaginal flora and STI-causing organisms, (3) research on the pathogenesis of disease caused by organisms transmitted by sexual contact and associated syndromes or conditions, and (4) research on the innate arid adaptive immune responses of the of the genital tract in relation to STIs.